PAPILLOMAVIRUS HOST INTERACTION

描述：(申请人摘要)乳头瘤病毒(PV) 被证明与子宫颈癌、外阴癌、 阴茎和皮肤。对这些病毒感染的免疫力起着重要的作用 在疾病转归中的作用，但精确的病毒免疫靶点 预防感染和破坏活动性病变较差 特色化的。这个项目的长期目标是确定 病毒抗原和免疫效应细胞参与了一种成功的 对乳头瘤病毒感染的免疫反应。这样做的目的是 应用于检测人类早期两个阶段的免疫力 人乳头瘤病毒11型和棉尾兔乳头瘤病毒 (CRPV)感染。第一种是以抗体介导的病毒为代表 中和，主要针对表面构象， 位于亚型多变区的类型特异性表位 乳头瘤病毒L1蛋白。第二种是细胞免疫。 早期病毒蛋白的表位存在于受感染的上皮细胞中。 需要检验的中心假设是对乳头瘤病毒的免疫力 蛋白质可以导致疾病的保护和解决。这个 这项研究背后的理论基础是，对病毒免疫的研究将 为保护性疫苗的设计提供必要的信息 人乳头瘤病毒感染的免疫治疗干预。要完成以下任务 本申请的目标，申请人将追求两个具体的 目标：(1)定义构象和构象组分的性质 乳头瘤病毒病毒粒子上的线性中和表位，以及(2) 确定乳头瘤病毒早期蛋白在诱导中的作用 对CRPV诱导的乳头状瘤的免疫力。在完成这项工作后 在研究中，他希望绘制出几个关键的氨基酸残基 由一个小组识别的HPV-11和CRPV病毒粒子 中和单抗(N-MAb)，并已确定 哪些CRPV早期病毒蛋白参与增强对CRPV的免疫力 乳头状瘤消退法测量乳头状瘤。此外，他还计划 将注意力集中在交叉反应、抗原性较低或 他的几个N-MAb识别的“二级”中和表位。 这些后一种表位可能是更广泛的 有效的(即改良的)VLP疫苗。定义主要保护措施 光伏病毒粒子上的病毒表位和早期病毒蛋白 乳头瘤病毒感染的细胞将是有效规划的关键 免疫治疗这种传染病的免疫治疗方法

DESCRIPTION: (Applicant's Abstract) Papillomaviruses (PVs) have been shown to contribute to the pathogenesis of cancer of the cervix, vulva, penis and skin. Immunity to these viral infections plays a significant role in disease outcome, but the precise viral targets of immunity for prevention of infection and destruction of active lesions are poorly characterized. The long-range goal of this project is to determine which viral antigens and immune effector cells are involved in a successful immune response to papillomavirus infection. The objective of this application is to examine immunity during two early stages of human papillomavirus type 11 (HPV-11) and cottontail rabbit papillomavirus (CRPV) infection. The first is represented by antibody-mediated virus neutralization, which predominantly targets surface conformational, type-specific epitopes located in the hypervariable regions of papillomavirus L1 proteins. The second is cell-mediated immunity to epitopes on early viral proteins present in infected epithelial cells. The central hypothesis to be tested is that immunity to papillomavirus proteins can lead to protection and resolution of the disease. The rationale behind the research is that studies on viral immunity will provide essential information for the design of protective vaccines and immuno-therapeutic interventions for HPV infections. To accomplish the objectives of this application, the applicant will pursue two Specific Aims: (1) define the nature of the components of conformational and linear neutralizing epitopes on papillomavirus virions, and (2) determine the role of the papillomavirus early proteins in the induction of immunity to CRPV-induced papillomas. At the completion of this research, he expects to have mapped several critical amino acid residues on HPV-11 and CRPV virions that are recognized by a panel of neutralizing monoclonal antibodies (N-MAbs), and to have determined which CRPV early viral proteins are involved in increased immunity to papillomas as measured by papilloma regression. In addition, he plans to focus attention on mapping of cross-reactive, less-antigenic or "secondary" neutralizing epitopes recognized by several of his N-MAbs. These latter epitopes may be an essential component of a more broadly effective (i.e., modified) VLP vaccine. Defining the major protective viral epitopes on PV virions and on the early viral proteins in papillomavirus-infected cells will be key to planning effective immunotherapeutic management of this infectious disease.